Ureteral stent with drug-releasing structure

ABSTRACT

According to one aspect of the present disclosure, ureteral stents are provided that comprise an elongated stent body, at least one deployable retention structure, and at least one sleeve and/or sheet of drug-releasing material. In various embodiments, at least one sleeve and/or sheet of drug-releasing material is deployed concurrently with the deployment of at least one deployable retention structure. The ureteral stents of the present disclosure are adapted to release the urologically beneficial drug into a subject.

STATEMENT OF RELATED APPLICATION

This application claims the benefit of U.S. Ser. No. 61/758,464, filedJan. 30, 2013 and entitled “URETERAL STENT WITH DRUG-RELEASINGSTRUCTURE,” which is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates generally to ureteral stents, and moreparticularly to ureteral stents which release drugs within the body of apatient.

BACKGROUND OF THE INVENTION

Ureteral stents are widely used to facilitate drainage in the upperurinary tract (e.g., from the kidney to the bladder), for example,following ureteroscopy, endourerotomies, and endopyelotomy for ureteralstrictures, as well as in other instances where ureteral obstruction mayoccur, for example, following lithotripsy.

A schematic diagram of a stent 10 in accordance with the prior art isschematically illustrated in FIG. 1. The stent 10 comprises an elongatedstent body in the form of a tubular polymeric extrusion including arenal coil 14, bladder coil 16, and a substantially linear shaft 12between the coils 14, 16. The stent 10 shown is further provided withthe following: (a) a tapered distal tip 10 k, to aid insertion, (b)multiple side ports 18 (one numbered), which are arranged in a spiralpattern along the length of the stent body to promote drainage, (c)graduation marks 13 (one illustrated), which are used for visualizationby the physician to know when the appropriate length of stent has beeninserted into the ureter, and (d) a Nylon suture 22, which aids inpositioning and withdrawal of the stent, is provided at the proximal end10 b of the stent, as is known in that art. During placement, theureteral stent 10 may be placed over a guide wire, through a cystoscopeand advanced into position with a positioner.

Referring now to FIGS. 1 and 2, once the distal (kidney) end 10 k of thestent is advanced into the kidney 19, the guide wire is removed,allowing the coils 14, 16 to form in the kidney 19 and bladder 20. Asshown in FIG. 2, the stent 10 extends through the ureteral orifice 21 aand into the bladder 20. For clarity, the ureter entering bladder 20through the opposite ureteral orifice 21 b is not shown.

Such stents, however, are commonly associated with pain and discomfortin the bladder and flank area after insertion. One way to minimize painand discomfort is to orally administer drugs to the patient. Commonlyprescribed oral drugs are opioid analgesia (e.g. Vicodin® andPercocet®), which are controlled substances and have the potential forabuse by patients.

Another way to address pain and discomfort is to release a therapeuticagent from the ureteral stent. See Pub. Nos. US 2003/0224033 to Li etal., US 2006/0264912 to McIntyre et al., US 2009/0187254 to Deal eatal., and US 2009/0248169 to Li et al.

SUMMARY OF THE INVENTION

According to one aspect of the invention, ureteral stents are providedthat comprise an elongated stent body, at least one deployable retentionstructure, and at least one sleeve of drug-releasing material.

According to another aspect of the invention, ureteral stents areprovided that comprise an elongated stent body, at least one deployableretention structure, and at least one sheet of drug-releasing material.In various embodiments, at least one sheet of drug-releasing material isdeployed concurrently with the deployment of at least one deployableretention structure.

The ureteral stents of the present disclosure are adapted to release theurologically beneficial drug into the subject.

Other aspects of the invention pertain to methods of forming such stentsand methods of using such stents.

These and other aspects, as well as various embodiments and advantagesof the present invention will become immediately apparent to those ofordinary skill in the art upon review of the Detailed Description andany claims to follow.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a side view of a ureteral stent, in accordance with the priorart.

FIG. 2 shows the ureteral stent of FIG. 1 as positioned within the body.

FIG. 3A is a schematic illustration of the kidney end of a ureteralstent, in accordance with an embodiment of the invention.

FIG. 3B is a schematic illustration of the kidney end of a ureteralstent, in accordance with another embodiment of the invention.

FIG. 4 is a cross-section taken along line 4-4 in FIG. 3A or FIG. 3B.

FIG. 5 is a schematic illustration of the kidney end of a ureteralstent, in accordance with another embodiment of the invention.

FIG. 6 is a cross-section taken along line 6-6 in FIG. 5.

FIG. 7 is a schematic illustration of a ureteral stent that comprisesdeployed drug-releasing sheets in conjunction with kidney and bladderretention coils, in accordance with an embodiment of the invention.

FIG. 8 is a schematic illustration of a ureteral stent that comprisesdeployed drug-releasing sheets in conjunction with kidney and bladderretention coils, in accordance with another embodiment of the invention.

FIG. 9 is a schematic illustration of the kidney end of a ureteralstent, in accordance with an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

A more complete understanding of the present invention is available byreference to the following detailed description of numerous aspects andembodiments of the invention. The detailed description of the inventionwhich follows is intended to illustrate but not limit the invention.

According to one aspect of the present disclosure, ureteral stents areprovided that comprise an elongated stent body, at least one deployableretention structure (e.g., a kidney coil, a bladder coil, or both), andat least one sleeve of drug-releasing material (also referred to hereinas a “drug-releasing sleeve”).

For example, FIGS. 3A and 3B are schematic illustrations of a kidneycoil portion 314 of ureteral stent 310 in linear form, in accordancewith two embodiments of the present disclosure. A kidney coil portion314 may be placed in substantially linear form, for example, by placingthe stent 310 over a guidewire (not shown), with the kidney coil portion314 returning to its naturally coiled shape upon removal of theguidewire (and thus removal of the straightening force associated withthe guidewire). Disposed over the kidney coil portion 314 is flexibledrug-releasing sleeve 313. The drug releasing sleeve 313 may be openended as shown in 3A or closed ended as shown in FIG. 3B (although asmall hole may be formed in the sleeve of FIG. 3B to allow for theinsertion of a guidewire). FIG. 4 is a cross-section taken along line4-4 in FIG. 3A or FIG. 3B, showing the sleeve 313 disposed over thekidney coil portion 314.

The drug-releasing sleeve may be disposed over any portion of the stentor all of the stent. For example, one or more drug-releasing sleeves maybe disposed over any combination of one or more of the followinglocations, among others: (a) disposed over a kidney coil portion of aureteral stent (see, e.g., FIGS. 3A and 3B), (b) disposed over a bladdercoil portion of a ureteral stent, and (c) disposed over the shaftportion lying between the coils. In some embodiments, one stent may havemultiple drug-releasing sleeves, which may contain the same or differenttherapeutic agents (e.g., selected from those described below, amongothers).

The use of drug-releasing sleeves provides a health care professional(e.g., a urologist) with an option to select one or more drug-releasingsleeves from a number of available drug-releasing sleeves, which maydiffer, for example, based on one or more the following characteristics,among others: (a) the type of therapeutic agent in the sleeves, (b) theconcentration of therapeutic agent in the sleeves, (c) the thickness ofthe sleeves and (d) the length of the sleeves. For example, in someembodiments, a drug-releasing sleeve with a first therapeutic agent maybe selected for use over a kidney coil portion of a ureteral stent and adrug-releasing sleeve with a second differing therapeutic agent may beselected for use over a bladder coil portion of the ureteral stent. Insome embodiments, drug-releasing sleeves are provided which are marked(e.g., labeled, color-coded or otherwise visually identifiable) toreflect the particular characteristics of the sleeve.

In some embodiments, the sleeve may be provided on the stent in the formof a layer or coating, for instance, during the manufacturing process.

The sleeve may be a solid film (which may include one or more layers),or it may be in the form of a film with a number of openings formedthere in, or it may be formed from one or more filaments, for example,being in the form of a mesh, web, netting, and so forth.

Typically, the drug-releasing sleeve may have an internal diameterranging, for example, from 1 mm to 4 mm (e.g., from 1 to 2 to 3 to 4 mm)and a length ranging, for example, from 2 to 500 mm (e.g., from 2 to 5to 10 to 25 to 50 to 100 to 250 to 500 mm in length), among othervalues. Typical thicknesses of the drug-releasing sleeve may range, forexample, between 50 and 200 μm (e.g., 50 to 75 to 100 to 150 to 200 μm),among other values.

In certain embodiments, the drug-releasing sleeve may be formed from anelastic material which allows the drug-releasing sleeve to be firmlysecured to the ureteral stent upon expansion and contraction, aheat-shrinkable material which allows the drug-releasing sleeve to befirmly secured to the ureteral stent upon application of heat, and soforth.

According to another aspect of the present disclosure, ureteral stentsare provided that comprise an elongated stent body, at least onedeployable retention structure, and at least one sheet of drug-releasingmaterial (also referred to herein as a “drug-releasing sheet”). Invarious embodiments, at least one sheet of drug-releasing material isdeployed (e.g., furled, unfolded or otherwise spread out) concurrentlywith the deployment of at least one deployable retention structure.

As used herein a “sheet” of material is one whose length and width areat least 10 times greater than its thickness, for example, one whoselength and width are each 10 to 25 to 50 to 100 or more times thethickness. As used herein, a sheet of material may be a solid film(which may include one or more layers), or it may be in the form of asolid film with a number of openings formed there in, or it may beformed from one or more filaments, for example, being in the form of amesh, web, netting, and so forth.

Sheets in accordance with the present disclosure may have at least oneedge that is connected to, or that is configured to be connected to, aureteral stent (e.g., to a stent body and/or retention member) and atleast one other edge that is not attached to any portion of the stent.

For example, FIG. 5 is a schematic illustration of a kidney coil portion514 of ureteral stent 510 in linear form, in accordance with anembodiment of the present disclosure. As noted above, the kidney coilportion 514 may be placed in substantially linear form, for example, byplacing the stent 510 over a guidewire (not shown), with the kidney coilportion 514 returning to its naturally coiled shape upon removal of theguidewire. Disposed over the kidney coil portion 514 is a flexiblesleeve 513, which may be a drug-releasing sleeve or which may contain notherapeutic agent. Associated with the sleeve 513 and disposed along itslength is a drug-releasing sheet 515. The drug-releasing sheet 515 maybe associated with the sleeve 513 by affixing an edge of the sheet 515to the sleeve 513 using a suitable adhesive or by co-forming the sheet515 and sleeve 513 (e.g., by extrusion or by injection molding). FIG. 6is a cross-section taken along line 6-6 in FIG. 5, showing the sleeve513 with attached drug-releasing sheet 515 disposed over the kidney coilportion 514. The sleeve 513 is open ended as shown in FIG. 5, but mayalso be closed ended as shown in FIG. 3A.

Although the drug-releasing sheet 515 is attached to the stent 510 via asleeve 513 in FIG. 5, in other embodiments, the sheet 515 may be securedto the stent, for example, by using a suitable adhesive whereby an edgeof the sheet 515 is directly attached to the stent 510, by using asnap-fit mechanism or locket' fit mechanism, or by co-forming the stentand sleeve (e.g., by extrusion or injection molding). Moreover, while asingle sheet 515 is shown, multiple smaller sheets (e.g., in the form ofmultiple strips, tassles, etc.) may be employed.

Moreover, although the drug-releasing sheet 515 and sleeve 513 are shownattached to a kidney coil portion of a ureteral stent in FIG. 5, adrug-releasing sleeve may also be secured various other portions of thestent or to the entire stent, as noted above.

Typically, the width of the drug releasing sheets may range, forexample, from 2 to 15 mm (e.g., from 2 to 5 to 10 to 15 mm), among othervalues, and the length of the drug releasing sheets may range, forexample, from 5 to 500 mm (e.g., from 5 to 10 to 20 to 50 to 100 to 200to 500 mm in length), respectively, among other values. Typicalthicknesses of the drug releasing sheet range, for example, between 50and 200 μm (e.g., 50 to 75 to 100 to 150 to 200 μm), among other values.

Although a portion of the drug-releasing sheet (e.g., an edge) istypically attached to a retention structure in the devices of thepresent disclosure, other portions of the drug-releasing sheet arefreestanding, allowing the sheet to be deployed (e.g., furled, unfoldedor otherwise spread out) in the body.

The drug-releasing sleeves and/or sheets described herein preferablycomprise a biodisintegrable material. As used herein a“biodisintegrable” material is one that biodisintegrates (e.g.,dissolves, biodegrades, bioerodes, etc.) once placed in the body. Thus,the sleeve and/or sheet of material may be, for example, soluble inurine and/or biodegraded in urine. Typically, biodisintegration of thesleeve and/or sheet material occurs over a period within the range of,for example, from 12 hours to 30 days (e.g., from 0.5 to 1 to 2 to 5 to10 to 20 to 30 days), among other values.

In one aspect, the present disclosure provides ureteral stents that areadapted to release one or more urologically beneficial drugs inpharmaceutically effective amounts. For example, such agents may beprovided in amounts effective to achieve the following benefits, amongothers: (a) the relief of pain and/or discomfort associated with theureteral stent, (b) treatment of a disease or condition associated withthe kidney, ureter and/or bladder, such as cancer, among others, (c)stone dissolution, (d) ureteral wall relaxation, and (e) the preventionof infection, among other benefits. As used herein, “treatment” refersto the prevention of a disease or condition, the reduction orelimination of symptoms associated with a disease or condition, or thesubstantial or complete elimination of a disease or condition. Preferredsubjects are vertebrate subjects, more preferably mammalian subjects andmore preferably human subjects, pets and livestock.

In some aspects, drug released from a sleeve and/or sheet associatedwith the bladder retention structure may be different from the drugreleased from a sleeve and/or sheet associated with the kidney retentionstructure. For example, one urologically beneficial drug may be releasedin the kidney to address stent pain, discomfort and flank pain in theupper urinary tract, while another urologically beneficial drug may bereleased into the bladder to address infection and/or biofilm formation,or to treat bladder cancer.

In some aspects, multiple drugs (e.g., any combination of two or moredrugs selected from drugs having analgesic activity, muscle relaxantactivity, anti-spasmodic activity, anti-inflammatory activity,anti-cancer activity, anti-microbial activity, etc.) may be releasedfrom a single device component. For example, multiple drugs may bereleased from a sleeve and/or sheet associated with the bladderretention structure, or multiple drugs may be released from a sleeveand/or sheet associated with the kidney retention structure, or both. Ina specific example, because drug released in the kidney eventually flowsdown the ureter and into the bladder, one or more drugs to address stentpain, discomfort and flank pain in the upper urinary tract and one ormore drugs to address infection, cancer and/or biofilm formation may bereleased from a sleeve and/or sheet associated with the kidney retentionstructure.

The retention structure may take on a particular beneficial shape invivo, for example, upon removal of a guide wire and/or emergence from achannel such as the working channel of an endoscope (e.g., due torebound of a material having a shape memory) or upon activation by aphysician. For example, in some embodiments the retention structure mayhave a shape memory that causes the retention element to take on anon-linear form in the body, for example, a loop, coil or corkscrewconfiguration, among others. In other embodiments, the retentionstructure may comprise a plurality of structural elements that expandradially (e.g., due to shape memory), for example, an umbrella-shaped orspheroidal configuration, among various others. Such constructions allowthe ureteral stent to be held in place in the urinary tract bydeployment of a retention structure in the kidney (e.g., in the renalcalyx and/or renal pelvis), the bladder, or both.

As noted above, in one aspect, the present disclosure provides ureteralstents that comprise an elongated stent body, at least one deployableretention structure, and at least one sleeve and/or sheet ofdrug-releasing material. As will be seen from the Figures describedbelow, in various embodiments, at least one sheet of drug-releasingmaterial is deployed (e.g., furled, unfolded or otherwise spread out)concurrently with the deployment of at least one deployable retentionstructure.

For example, turning to FIG. 7, there is schematically illustratedtherein a stent 710 in accordance with the present disclosure. The stent710 comprises an elongated stent body in the form of a tubular polymericextrusion including a renal coil 714, bladder coil 716, and asubstantially linear shaft 712 between the coils 714, 716. The stent 720shown is further provided with a tapered distal tip 710 k, to aidinsertion, and multiple side ports 718 (one numbered), which arearranged along the length of the stent body to promote drainage. A sheetof drug-releasing material 715 k is spread out within the kidney coil714 upon formation of the kidney coil 714 in vivo. A sheet 715 k likethat shown may be created by forming a coil (e.g., by removing a guidewire) from a kidney coil portion 514 of a ureteral stent 510 analogousto that described in conjunction with FIGS. 5 and 6, such that thedrug-releasing sheet 515 like that described in conjunction with FIGS. 5and 6 rearranges its shape to form a sheet of drug-releasing material715 k like that shown in FIG. 7. A sheet of drug-releasing material 715b may be likewise spread out within the bladder coil 716 upon formationof the bladder coil 716 in vivo.

As another example, turning to FIG. 8, a sheet of drug-releasingmaterial 715 k (in the form of an elastic web) is spread out within thekidney coil 814 upon formation of the kidney coil 814 in vivo.Similarly, a sheet of drug-releasing material 815 b (also in the form ofan elastic web) is spread out within the bladder coil 816 upon formationof the bladder coil 816 in vivo. By forming the sheets of drug-releasingmaterial 815 k and 815 b using an elastic material (e.g., elasticfilaments), the kidney coil 814 and bladder coil 816 may be straightenedsuch that the stent can be deployed, for instance, over a guidewire(e.g., through a cystoscope).

The sheet of drug-releasing material, however, does not need to beelastic in nature. For example, in some embodiments, the sheet ofdrug-releasing material may not be flat (e.g., it may be wrinkled) upondeployment in the body.

While a circular coil is shown in FIGS. 7 and 8, retention structures ina variety of other shapes may be provided including oval coils, andpolygonal coils, among others. The two coils may be of the same diameteror different in diameter.

Numerous other designs may be employed whereby drug-releasing sleevesand/or sheets of material may be deployed in conjunction with kidneyretention structures, bladder retention structures, or both.

As one specific example, an end of a ureteral stent, for instance, adistal (kidney) end 910 k, is schematically shown in FIG. 9 and includesa retention structure 914 that is formed from a plurality of elongatedstructural elements and a sheet of drug-releasing material 915associated with the retention structure 914. The structural elementsforming the retention structure 914 may be elastic materials with ashape memory (e.g., a shape memory polymer, or a shape memory metal suchas nitinol, etc.) and can be compressed within a delivery tube (e.g., acystoscope). When forced from the delivery tube at the time of delivery,the structural elements expand to form a fully deployed retentionstructure 914 shown in FIG. 9. While a spheroidal retention structure isshown in FIG. 9 (specifically a prolate spheroid, although oblatespheroids and spheres are also useful), retention structures in avariety of other shapes may be formed.

The sheet of drug-releasing material 915 may be elastic or inelastic incharacter. Where elastic, the sheet 915 may be stretched into anexpanded form upon deployment of the retention structure 914. Whereinelastic, the sheet 915 may be folded (analogous to fabric in anumbrella) and unfurled upon deployment of the retention structure 914 ormay be flat during placement and wrinkled upon deployment.

While the retention structure 914 and drug-releasing sheet 915 shown inFIG. 9 correspond to the kidney end of a ureteral stent, an analogousstructure could be employed at the bladder end of the device, or at boththe kidney and bladder ends of the device.

The stent body and retention structures may be formed from a variety ofmetallic and non-metallic materials, with polymeric materials beingpreferred in certain embodiments, more preferably polymeric materialscapable of being provided with a shape memory.

As used herein, “polymers” are molecules containing multiple copies(e.g., from 2 to 5 to 10 to 25 to 50 to 100 to 250 to 500 to 1000 ormore copies) of one or more constitutional units, commonly referred toas monomers. As used herein, the term “monomers” may refer to the freemonomers and those that are incorporated into polymers, with thedistinction being clear from the context in which the term is used.

Polymers may take on a number of configurations, which may be selected,for example, from cyclic, linear, branched and networked (e.g.,crosslinked) configurations. Branched configurations include star-shapedconfigurations (e.g., configurations in which three or more chainsemanate from a single branch point, for instance an initiator moleculeor a linking molecule), comb configurations (e.g., configurations havinga main chain and a plurality of side chains), dendritic configurations(e.g., arborescent and hyperbranched polymers), networked (e.g.,crosslinked) configurations, and so forth.

As used herein, “homopolymers” are polymers that contain multiple copiesof a single constitutional unit. “Copolymers” are polymers that containmultiple copies of at least two dissimilar constitutional units,examples of which include random, statistical, gradient, periodic (e.g.,alternating) and block copolymers. As used herein, “block copolymers”are copolymers that contain two or more polymer blocks that differ incomposition, for instance, because a constitutional unit (i.e., monomer)is found in one polymer block that is not found in another polymerblock. As used herein, a “polymer block” is a grouping of constitutionalunits (e.g., 2 to 5 to 10 to 25 to 50 to 100 to 250 to 500 to 1000 ormore units). Blocks can be branched or unbranched, and they may benetworked (e.g., by crosslinking) Blocks can contain a single type ofconstitutional unit (also referred to herein as “homopolymeric blocks”)or multiple types of constitutional units (also referred to herein as“copolymeric blocks”) which may be provided, for example, in a random,statistical, gradient, or periodic (e.g., alternating) distribution.

In embodiments like those shown in FIGS. 3A, 3B, 5, 7 and 8, where theretention structures (i.e., coils) are formed from the stent body, thestent body may be formed from material having a single composition.Alternatively, the stent body may be formed of a material of varyingcomposition, for instance, varying from a relatively hard material foruse in the kidney retention structure and a relatively soft materialbeing used for the bladder structure, with the substantially linear(ureter) section displaying either a gradual composition change alongits length or an abrupt composition change at some point along itslength.

Polymers used for forming the stent body and retention structures of thepresent disclosure include biodisintegrable and biostable polymers, moretypically biostable polymers, which may be selected, for example, fromvarious thermoplastic polymers, elastomeric polymers, andthermoplastic-elastomeric polymers.

Polymers for use in the stent body and retention structures of thepresent disclosure may be selected, for example, from polycarbonates,silicone polymers, polyurethanes, poly(ether-block-amides), and alkenepolymers, among others.

Polycarbonates are derived from the reaction of carbonic acidderivatives with aromatic, aliphatic, or mixed diols. They may beproduced, for example, by the reaction of phosgene with a diol in thepresence of an appropriate hydrogen chloride receptor or by a melttransesterification reaction between a diol and a carbonate ester.Polycarbonates can be made from a wide variety of starting materials.For example, a common polycarbonate, bisphenol A polycarbonate, is apolycarbonate made by reacting bisphenol A with phosgene bycondensation. For further information, see, e.g., U.S. Pat. No.5,580,924 and the references cited therein.

Silicone polymers (also referred to as polysiloxanes) are polymerscomprising one or more types of siloxane units,

where R₁ and R₂ can be the same or different and may be selected fromlinear, branched and cyclic alkyl groups, aromatic groups andalky-aromatic groups, for example, having from 1 to 10 carbon atoms, andhaving 5 or more, typically 10 to 25 to 50 to 100 to 250 to 500 to 1000or more siloxane units. Examples include polydimethylsiloxane,polydiethylsiloxane, polymethylethylsiloxane, polymethylphenylsiloxane,and polydiphenylsiloxane, among many others. Such polymers are commonlycrosslinked.

In general, polyurethanes are a family of polymers that are synthesizedfrom polyfunctional isocyanates (e.g., diisocyanates, including bothaliphatic and aromatic diisocyanates) and polyols (also, referred to asmacroglycols, e.g., macrodiols). Commonly employed macroglycols includepolyester glycols, polyether glycols, polycarbonate glycols andpolyolefin glycols. Typically, aliphatic or aromatic diols are alsoemployed as chain extenders, for example, to impart the useful physicalproperties. Examples of diol chain extenders include butane diol,pentane diol, hexane diol, heptane diol, benzene dimethanol,hydraquinone diethanol and ethylene glycol. Polyurethanes are commonlyclassified based on the type of macroglycol employed, with thosecontaining polyester glycols being referred to as polyesterpolyurethanes, those containing polyether glycols being referred to aspolyether polyurethanes, those containing polycarbonate glycols beingreferred to as polycarbonate polyurethanes and those containingpolyolefin glycols being referred to as polyolefin polyurethanes

Polyurethanes are also commonly designated as aromatic or aliphatic onthe basis of the chemical nature of the diisocyanate component in theirformulation. For example, U.S. Patent App. No. 2004/0131863 to Belliveauet al. describes aliphatic polycarbonate polyurethanes which are thereaction products of (a) a hydroxyl terminated polycarbonate, (b) analiphatic diisocyanate and (c) a lower aliphatic chain extender.Hydroxyl terminated polycarbonate polyol may be prepared by reacting aglycol with a carbonate, as disclosed in U.S. Pat. No. 4,131,731.Suitable aliphatic diisocyanates include hexamethylene diisocyanate(HDI), isophorone diisocyanate (IPDI), trimethyl hexamethylenediisocyanate (TMHDI), dicyclohexyl methane diisocyanate (HMDI), anddimer acid diisocyanate (DDI), with HMDI said to be preferred. Suitablechain extenders include lower aliphatic glycols having from about 2 toabout 10 carbon atoms, such as, for instance ethylene glycol, diethyleneglycol, propylene glycol, dipropylene glycol, 1,4-butanediol,1,6-hexanediol, 1,3-butanediol, 1,5-pentanediol,1,4-cyclohexanedimethanol hydroquinone di(hydroxyethyl) ether,neopentyglycol, and the like, with 1,4-butanediol said to be preferred.

Another group of polymers are block copolymers comprising polyetherblocks (i.e., polymer blocks containing multiple C—O—C linkages) andpolyamide blocks (i.e., polymer blocks containing multiple —NH—CO—linkages), sometimes referred to as polyether-block-amides orpoly(ether-b-amides). A few specific examples of polyether blocksinclude homopolymeric and copolymeric blocks of the formulas(a)-[R₁—O—]_(n)— or (b) -[R₁—O—R₂—O]_(n)—, where R₁ and R₂ can be thesame or different and may be selected from linear, branched and cyclicalkyl groups, aromatic groups and alky-aromatic groups, for example,having from 1 to 10 carbon atoms (more typically linear or branchedalkyl groups having from 1 to 6 carbons) and where n is an integer of 5or more, typically 10 to 25 to 50 to 100 to 250 to 500 to 1000 or more.Polyethers may be formed, for example, from ring opening additionpolymerization of cyclic ethers, such as ethylene oxide, whereR₁═R₂=dimethylene (i.e., [—(CH₂₎ ₂—O—]_(n)), which is commonly referredto as polyethylene glycol or as polyethylene oxide), trimethylene oxide,where R₁═R₂=trimethylene (i.e., [—(CH₂)₃—O—]_(n)), propylene oxide,where R₁═R₂=methyl substituted dimethylene (i.e., [—CH₂CH₂(CH₃)—O—]_(n),referred to as polypropylene glycol or polypropylene oxide), andtetrahydrofuran, where R₁═R₂=tetramethylene (i.e.,—[(CH₂)₄—O]—_(n),which is referred to as polytetramethylene glycol, polytetramethyleneoxide (PTMO), or terathane). Examples of polyamide blocks, which may beprovided, for example, as homopolymeric or copolymeric blocks, includepolyamides of the formula —[R₃—NH—CO]_(m)— or —[NH—R₃—NH—CO—R₄—CO]_(m)—,where R₃ and R₄ can be the same or different and may be selected fromlinear, branched and cyclic alkyl groups, aromatic groups andalky-aromatic groups, for example, of 1 to 20 carbon atoms (moretypically linear or branched alkyl groups having from 1 to 15 carbons,such as methyl, ethyl, propyl, isopropyl, and so forth) and where m isan integer of 5 or more, typically 10 to 25 to 50 to 100 to 250 to 500to 1000 or more. Specific examples include nylons, such as nylon 6,nylon 4/6, nylon 6/6, nylon 6/10, nylon 6/12, nylon 11 and nylon 12. Aspecific example of a polyether-polyamide block copolymer ispoly(tetramethylene oxide)-b-polyamide-12 block copolymer, availablefrom Elf Atochem as PEBAX.

Further polymers include polyalkene homopolymers and copolymers withthemselves and with various other monomers including those selected fromvinyl aromatic monomers such as styrene, acrylic acid, methacrylic acid,and vinyl acetate. Examples of alkene monomers include ethylene,propylene, isobutylene, 1-butene, 1-pentene, 4-methyl-1-pentene, dienessuch as 1,3-butadiene, 2-methyl-1,3-butadiene (isoprene),2,3-dimethyl-1,3-butadiene, 2-ethyl-1,3-butadiene, 1,3-pentadiene,2-methyl-1,3-pentadiene, 4-butyl-1,3-pentadiene,2,3-dibutyl-1,3-pentadiene, 2-ethyl-1,3-pentadiene, 1,3-hexadiene,1,3-octadiene, and 3-butyl-1,3-octadiene, among others. Specificexamples of alkene copolymers include, poly(ethylene-co-vinyl acetate)(EVA), poly(ethylene-co-methacrylic acid), poly(ethylene-co-acrylicacid), and poly(isobutylene-co-styrene), among many others.

Poly(isobutylene-co-styrene) copolymers includepoly(styrene-b-isobutylene-b-styrene) triblock copolymers (SIBS), whichare described in U.S. Pat. No. 6,545,097 to Pinchuk et al. SIBS is athermoplastic elastomer.

Among EVA copolymers are included random and other copolymers having avinyl acetate weight percent ratio of from about 0.5% to 1% to 2% to 5%to 15% to 20% to 30% to 40% or more. In general, the higher the vinylacetate content, the lower the stiffness and Durometer of the EVA.

For example, EVA having a high vinyl acetate content (e.g., 25 to 35 wt% or more) and decreased stiffness may be employed in the portion of thestent occupying the bladder for increased comfort, while EVA having alow vinyl acetate content (e.g., 10 to 20 wt % or less) and increasedstiffness may be employed in the portion occupying the kidney for goodretention character. The portion occupying the ureter may be of highvinyl acetate content, low vinyl acetate content or intermediate vinylacetate content (e.g., 20 to 25 wt %); or the portion occupying theureter gradually or abruptly transition from the high vinyl acetatecontent of the bladder portion to the low vinyl acetate content of thekidney portion.

As previously noted, materials for forming the drug-releasing sleevesand/or sheets of the present disclosure may be elastic or inelastic incharacter. Materials for forming the drug-releasing sleeves and/orsheets of the present disclosure may be inorganic or organic incharacter. Materials for forming the drug-releasing sleeves and/orsheets of the present disclosure may be biostable or biodisintegrable incharacter.

In various embodiments, the drug-releasing sleeves and/or sheets arebiodisintegrable and organic in character, for example, comprising abiodisintegrable small molecule (non-polymeric) material such as a sugar(e.g., sucrose, lactose, etc.), fatty acid, or fatty acid ester, abiodisintegrable biopolymer such as a polysaccharide, polypeptide orprotein (e.g., alginate, chitosan, starch, gelatin, heparin, albumin,hyaluronic acid, etc.), or a biodisintegrable synthetic polymer.

Examples of biodisintegrable synthetic polymers include, for example,soluble synthetic polymers (e.g., low molecular EVA, etc.) andbiodegradable synthetic polymers which may be selected from suitablemembers of the following, among others: (a) polyester homopolymers andcopolymers such as polyglycolide, poly-L-lactide, poly-D-lactide,poly-D,L-lactide, poly(beta-hydroxybutyrate), poly-D-gluconate,poly-L-gluconate, poly-D,L-gluconate, poly(epsilon-caprolactone),poly(delta-valerolactone), poly(p-dioxanone), poly(trimethylenecarbonate), poly(lactide-co-glycolide),poly(lactide-co-delta-valerolactone),poly(lactide-co-epsilon-caprolactone), poly(L-lactide-co-beta-malicacid), poly(lactide-co-trimethylene carbonate),poly(glycolide-co-trimethylene carbonate),poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate),poly[1,3-bis(p-carboxyphenoxy)propane-co-sebacic acid], and poly(sebacicacid-co-fumaric acid), among others (b) polyanhydride homopolymers andcopolymers such as poly(adipic anhydride), poly(suberic anhydride),poly(sebacic anhydride), poly(dodecanedioic anhydride), poly(maleicanhydride), poly[1,3-bis(p-carboxyphenoxy)methane anhydride], andpoly[alpha,omega-bis(p-carboxyphenoxy)alkane anhydrides] such aspoly[1,3-bis(p-carboxyphenoxy)propane anhydride] andpoly[1,3-bis(p-carboxyphenoxy)hexane anhydride], among others; and (c)amino acid based homopolymers and copolymers including tyrosine-basedpolyarylates (e.g., copolymers of a diphenol and a diacid linked byester bonds, with diphenols selected, for instance, from ethyl, butyl,hexyl, octyl and benzyl esters of desaminotyrosyl-tyrosine and diacidsselected, for instance, from succinic, glutaric, adipic, suberic andsebacic acid), tyrosine-based polycarbonates (e.g., copolymers formed bythe condensation polymerization of phosgene and a diphenol selected, forinstance, from ethyl, butyl, hexyl, octyl and benzyl esters ofdesaminotyrosyl-tyrosine, among others), and leucine and lysine-basedpolyester-amides

In certain embodiments, a polymer that is both elastic andbiodisintegrable is employed. Elastic biodisintegrable polymers includethe following, among others: biodisintegrable block copolymerscomprising biodegradable polyesters, such as block copolymers comprisingpolycaprolactone (PCL) and poly-L-lactic acid (PLLA) blocks and blockcopolymers comprising 1,3-trimethylene carbonate (PTMC) andpoly-L-lactic acid (PLLA) blocks; biodisintegrable block copolymerscomprising biodegradable polyesters and polyethers such as blockcopolymers comprising polyethylene oxide (PEO) and poly-L-lactic acid(PLLA) blocks; biodisintegrable copolymers comprising polyacids andpolyols including biodisintegrable polymers comprising citric acid suchas poly(1,8-octanediol-co-citric acid) and poly(1,8-octanediol-co-malicacid-co-citric acid) and biodisintegrable polymers comprising sebacicacid such as poly(xylitol sebacate); and biodisintegrable polyurethanesincluding poly(ester-urethanes) such as poly(c-caprolactone-co-lactide)polyurethanes and poly(ether-ester-urethanes) suchpoly(c-caprolactone-co-lactide-co-ethylene oxide) polyurethanes.

In certain embodiments a polymer that is both heat shrinkable andbiodisintegrable is employed.

A variety of urologically beneficial drugs may be released from thedrug-releasing sleeves and/or sheets of the present disclosure.

As used herein, a “urologically beneficial drug” is an agent that issufficiently safe and effective for use in humans or animals whenreleased from an implantable or insertable urological device, inparticular, a ureteral stent. Urologically beneficial drugs includeagents that benefit the urinary tract (e.g., stone dissolution agents,ureteral wall relaxation agents, etc.) and agents that reduce sideeffects associated with ureteral stents, including pain or discomfortand infection, among other side effects.

In some embodiments, urologically beneficial drugs for use in thepresent disclosure have one or more of the following, among others:muscle relaxant activity (e.g., they have musculotropic relaxantproperties, smooth muscle relaxant properties, etc.), anti-spasmodicactivity, anti-inflammatory activity, analgesic activity, anti-canceractivity and anti-microbial activity.

Urologically beneficial drugs for use in the present disclosure may beselected, for example, from one or more suitable members of thefollowing, among others: alpha-adrenergic blockers, calcium channelblockers, beta-adrenergic agonists, bronchodilators (e.g., for musclerelaxant properties), nitric oxide donors, nitric oxide releasingcompounds, prostaglandins, corticosteroids, narcotic analgesic agents,non-narcotic analgesic agents, local anesthetic agents,antiproliferative agents and antineoplastic agents, among others, aswell as combinations thereof.

Examples of alpha-adrenergic blockers for use in the present disclosuremay be selected from suitable members of the following: alfuzosin,amosulalol, arotinilol, dapiprazole, doxazosin, ergoloid mesylates,fenspiride, idazoxan, indoramin, labetalol, manotepil, naftopidil,nicergoline, prazosin, tamsulosin, terazosin, tolazoline, trimazosin,and yohimbine, among others, as well as combinations andpharmaceutically acceptable salts, esters and other derivatives of thesame. Of these, tamsulosin, alfuzosin, doxazosin, prazosin, tamsulosinand terazosin are alpha-1-adrenergic blockers, of which tamsulosin andalfuzosin are selective alpha-1-adrenergic blockers.

Examples of calcium channel blockers for use in the present disclosuremay be selected from suitable members of the following: arylalkylamines(including phenylalkylamines) such as verapamil, gallopamil, bepridil,clentiazen, fendiline, mibefradil, prenylamine, semotiadil, andterodiline, benzothiazepines such as diltiazem; dihydropyridinederivatives (including 1,4-dihydropyridine derivatives) such asamlodipine, aranidipine, barnidipine, benidipine, cilnidipine,efonidipine, elgodipine, felodipine, isradipine, lacidipine,lercanidipine, manidipine, nicardipine, nifedipine, nilvadipine,nimodipine, nisoldipine and nitrendipine, piperazine derivatives such ascinnarizine, dotarizine, flunarizine, lidoflazine and lomerizine,calcium channel blockers such as bencyclane, etafenone, fantofarone,monatepil and perhexiline, among other calcium channel blockers, as wellas combinations and pharmaceutically acceptable salts, esters and otherderivatives of the same.

Examples of beta-adrenergic agonists for use in the present disclosuremay be selected from suitable members of the following: albuterol,bambuterol, bitolterol, carbuterol, clenbuterol, clorprenaline,denopamine, ephedrine, epinephrine, etafedrine, ethylnorepinephrine,fenoterol, formoterol, hexoprenaline, ibopamine, isoetharine,isoproterenol, mabuterol, metaproterenol, methoxyphenamine, oxyfedrine,pirbuterol, prenalterol, procaterol, protokylol, reproterol, rimiterol,ritodrine, salmerterol, soterenol, terbutaline, tretoquinol, tulobuteroland xamoterol, among others, as well as combinations andpharmaceutically acceptable salts, esters and other derivatives of thesame.

Examples of bronchodilators for use in the present disclosure may beselected from suitable members of the following: (a) ephedrinederivatives such as albuterol, bambuterol, bitolterol, carbuterol,clenbuterol, clorprenaline, dioxethedrine, ephedrine, epinephrine,eprozinol, etafedrine, ethylnorepinephrine, fenoterol, formoterol,hexoprenaline, isoetharine, isoproterenol, mabuterol, metaproterenol,n-methylephedrine, pirbuterol, procaterol, protokylol, reproterol,rimiterol, salmeterol, soterenol, terbutaline and tulobuterol, (b)quaternary ammonium compounds such as bevonium methyl sulfate,flutropium bromide, ipratropium bromide, oxitropium bromide andtiotropium bromide, (c) xanthine derivatives such as acefylline,acefylline piperazine, ambuphylline, aminophylline, bamifylline, cholinetheophyllinate, doxofylline, dyphylline, etamiphyllin, etofylline,guaithylline, proxyphylline, theobromine, 1-theobromineacetic acid andtheophylline, and (d) other bronchodilators such as fenspiride,medibazine, methoxyphenanime and tretoquinol, among others, as well ascombinations and pharmaceutically acceptable salts, esters and otherderivatives of the forgoing.

Examples of nitric oxide donors/releasing molecules for use in thepresent disclosure may be selected from suitable members of thefollowing: inorganic nitrates/nitrites such as nitroglycerin, isosorbidedinitrate and amyl nitrite, inorganic nitroso compounds such as sodiumnitroprusside, sydnonimines such as molsidomine and linsidomine,nonoates such as diazenium diolates and NO adducts of alkanediamines,S-nitroso compounds including low molecular weight compounds (e.g.,S-nitroso derivatives of captopril, glutathione and N-acetylpenicillamine) and high molecular weight compounds (e.g., S-nitrosoderivatives of proteins, peptides, oligosaccharides, polysaccharides,synthetic polymers/oligomers and natural polymers/oligomers), as well asC-nitroso-compounds, O-nitroso-compounds, N-nitroso-compounds andL-arginine, among others, as well as pharmaceutically acceptable salts,esters and other derivatives of the same, and combinations of theforegoing.

Examples of prostaglandins and analogs thereof for use in the presentdisclosure may be selected from suitable members of the following:prostaglandins such as PGE1 and PGI2 and prostacyclin analogs such asciprostene, epoprostenol, carbacyclin, iloprost and beraprost, amongothers, as well as pharmaceutically acceptable salts, esters and otherderivatives of the same, and combinations of the foregoing.

Examples of corticosteroids for use in the present disclosure may beselected from suitable members of the following: betamethasone,cortisone, dexamethasone, deflazacort, hydrocortisone,methylprednisolone, prednisolone, prednisone and triamcinolone, amongothers, as well as combinations and pharmaceutically acceptable salts,esters and other derivatives of the same.

Examples of narcotic analgesic agents for use in the present disclosuremay be selected from suitable members of the following: codeine,morphine, fentanyl, meperidine, propoxyphene, levorphanol, oxycodone,oxymorphone, hydromorphone, pentazocine, and methadone, among others, aswell as combinations and pharmaceutically acceptable salts, esters andother derivatives of the same.

Examples of non-narcotic analgesic agents for use in the presentdisclosure may be selected from suitable members of the following:analgesic agents such as acetaminophen, and non-steroidalanti-inflammatory drugs such as aspirin, diflunisal, salsalate,ibuprofen, ketoprofen, naproxen indomethacin, celecoxib, valdecoxib,diclofenac, etodolac, fenoprofen, flurbiprofen, ketorolac,meclofenamate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam,sulindac, tolmetin, and valdecoxib, among others, as well ascombinations and pharmaceutically acceptable salts, esters and otherderivatives of the same.

Examples of local anesthetic agents for use in the present disclosuremay be selected from suitable members of the following: benzocaine,cocaine, lidocaine, mepivacaine, and novacaine, among others, as well ascombinations and pharmaceutically acceptable salts, esters and otherderivatives of the same.

Examples of antiproliferative/antineoplastic agents for use in thepresent disclosure may be selected from suitable members of thefollowing: antimetabolites such as purine analogs (e.g.,6-mercaptopurine or cladribine, which is a chlorinated purine nucleosideanalog, etc.), pyrimidine analogs (e.g., cytarabine, 5-fluorouracil,etc.) and methotrexate, nitrogen mustards, alkyl sulfonates,ethylenimines, antibiotics (e.g., daunorubicin, doxorubicin, etc.),nitrosoureas, cisplatin, agents affecting microtubule dynamics (e.g.,vinblastine, vincristine, colchicine, Epo D, paclitaxel, epothilone,etc.), caspase activators, proteasome inhibitors, angiogenesisinhibitors (e.g., endostatin, angiostatin, squalamine, etc.), olimusfamily drugs (e.g., sirolimus, everolimus, tacrolimus, zotarolimus,etc.), cerivastatin, flavopiridol and suramin, among others, as well ascombinations and pharmaceutically acceptable salts, esters and otherderivatives of the same.

Examples of antimicrobial agents for use in the present disclosure maybe selected, for example, from triclosan, chlorhexidine, nitrofurazone,benzalkonium chlorides, silver salts, silver particles, metallic silverand antibiotics, such as rifampin, gentamicin and minocycline, andcombinations thereof, among others.

Urologically beneficial drugs may be may be associated with the drugreleasing sleeves and/or sheets in various ways, including thefollowing, among others: (a) loaded in the interior (bulk) of the sleeveand/or sheet material, (b) bound to the surface of the sleeve and/orsheet material by covalent interactions and/or non-covalent interactions(e.g., interactions such as van der Waals forces, hydrophobicinteractions and/or electrostatic interactions, for instance,charge-charge interactions, charge-dipole interactions, anddipole-dipole interactions, including hydrogen bonding), (c) applied asa coating that covers all or a portion of the sleeve and/or sheetmaterial, (d) loaded in surface features (e.g., depressions) in thesleeve and/or sheet material, and (e) combinations of the forgoing.

Drug-releasing sleeves and/or sheets in accordance with the presentdisclosure may contain a wide range of urologically beneficial drugloadings, with the effective amount being readily determined by those ofordinary skill in the art. For example, the amount of urologicallybeneficial drug(s) associated with the drug-releasing sleeves and/orsheets may range, for example, from than 1 wt % or less to 2 wt % to 5wt % to 10 wt % to 25 wt % to 50 wt % or more.

The release of the one or more urologically beneficial drugs from thedrug-releasing sleeves and/or sheets will be affected by a number ofvariables. For example, for a given polymeric matrix material, therelease profile of the urologically beneficial drug will depend, forexample, upon the geometry of the drug-releasing sleeve and/or sheet(e.g., thickness, surface, area, etc.), upon the particular urologicallybeneficial drug(s) selected, upon the particular polymer(s) selected,and upon the relative amount of drug and matrix material, among otherfactors.

Ureteral stents in accordance with the present disclosure may alsocontain agents in addition to urologically beneficial agents. Forexample, imaging agents may be associated with one or more of the stentshaft, the retention structure(s) and the drug-eluting sleeve(s) and/orsheet(s).

For example, x-ray based fluoroscopy is a diagnostic imaging techniquethat allows real-time patient monitoring of motion within a patient. Tobe fluoroscopically visible, devices and/or compositions are typicallyrendered more absorptive of x-rays than the surrounding tissue (e.g.,radiopaque materials). In various embodiments of the present disclosure,this is accomplished by the use of contrast agents. Examples of contrastagents for use in connection with x-ray fluoroscopy include metals,metal salts and oxides (particularly bismuth salts and oxides), andiodinated compounds, among others. More specific examples of suchcontrast agents include tungsten, platinum, tantalum, iridium, gold, orother dense metal, barium sulfate, bismuth subcarbonate, bismuthtrioxide, bismuth oxychloride, metrizamide, iopamidol, iothalamatesodium, iodomide sodium, and meglumine, among others.

Ultrasound uses high frequency sound waves to create an image of livingtissue. A sound signal is sent out, and the reflected ultrasonic energy,or “echoes,” are used to create the image. Ultrasound imaging contrastagents are materials that enhance the image produced by ultrasoundequipment. Ultrasonic imaging contrast agents can be, for example,echogenic (i.e., materials that result in an increase in the reflectedultrasonic energy) or echolucent (i.e., materials that result in adecrease in the reflected ultrasonic energy). Suitable ultrasonicimaging contrast agents for use in connection with the presentdisclosure include solid particles ranging from about 0.01 to 50 micronsin largest dimension (e.g., the diameter, where spherical particles areutilized), more typically about 0.5 to 20 microns. Both inorganic andorganic particles can be used. Examples includemicroparticles/microspheres of calcium carbonate, hydroxyapatite,silica, poly(lactic acid), and poly(glycolic acid), among others.Microbubbles can also be used as ultrasonic imaging contrast agents, asis known in the imaging art.

Magnetic resonance imaging (MRI) produces images by differentiatingdetectable magnetic species in the portion of the body being imaged. Inthe case of ¹H MRI, the detectable species are protons (hydrogennuclei). In order to enhance the differentiation of detectable speciesin the area of interest from those in the surrounding environment,imaging contrast agents are often employed. These agents alter themagnetic environment of the detectable protons in the area of interestrelative to that of protons in the surrounding environment and therebyallow for enhanced contrast and better images of the area of interest.For contrast-enhanced MRI, it is desirable that the contrast agent havea large magnetic moment, with a relatively long electronic relaxationtime. Based upon these criteria, contrast agents such as Gd(III), Mn(II)and Fe(III) have been employed. Gadolinium(III) has the largest magneticmoment among these three and is, therefore, a widely-used paramagneticspecies to enhance contrast in MRI. Chelates of paramagnetic ions suchas Gd-DTPA (gadolinium ion chelated with the liganddiethylenetriaminepentaacetic acid) have been employed as MRI contrastagents. Chelation of the gadolinium or other paramagnetic ion isbelieved to reduce the toxicity of the paramagnetic metal by renderingit more biocompatible, and can assist in localizing the distribution ofthe contrast agent to the area of interest. Further information can befound, for example, in U.S. Patent Application No. 2003/0100830 entitled“Implantable or insertable medical devices visible under magneticresonance imaging.

In some embodiments, kits are provided in accordance with the presentdisclosure. Such kits may comprise, for example, two or more of thefollowing: (a) a ureteral stent, (b) a guidewire, (c) one or moredrug-releasing sleeves which can be applied to the stent and (d) one ormore drug-releasing sheets which can be applied to the stent. The kitsmay also include packaging and information as required by a governmentalregulatory agency that regulates pharmaceuticals and/or medical devices.The components of the kits may be provided in a sterile package forconvenient use by a health care professional.

Although various embodiments are specifically illustrated and describedherein, it will be appreciated that modifications and variations of thepresent invention are covered by the above teachings and are within thepurview of any appended claims without departing from the spirit andintended scope of the invention.

1. A ureteral stent comprising an elongated stent body, a deployableretention structure, and a drug-releasing member selected from (i) asleeve of drug-releasing material that is disposed over at least aportion of the deployable retention structure, (ii) a sheet ofdrug-releasing material that is attached to the deployable retentionstructure and (iii) a sheet of drug-releasing material connected to asleeve of material that is disposed over at least a portion of thedeployable retention structure.
 2. The ureteral stent of claim 1,comprising a sleeve of drug-releasing material that is disposed over atleast a portion of the deployable retention structure.
 3. The ureteralstent of claim 2, wherein the sleeve is a biodisintegrable sleeve. 4.The ureteral stent of claim 2, wherein the sleeve is a heat shrinkablesleeve.
 5. The ureteral stent of claim 2, wherein the sleeve ranges from1 to 4 mm in inner diameter, from 2 to 500 mm in length and from 50 to200 micrometers in thickness.
 6. The ureteral stent of claim 1,comprising a sheet of drug-releasing material that is attached to thedeployable retention structure.
 7. The ureteral stent of claim 6,wherein the sheet is a biodisintegrable sheet.
 8. The ureteral stent ofclaim 6, wherein the sheet is an elastic sheet.
 9. The ureteral stent ofclaim 6, wherein the sheet ranges from 2 to 20 mm in width, from 2 to500 mm in length and from 50 to 200 micrometers in thickness.
 10. Theureteral stent of claim 1, wherein the retention structure is in theform of a coil or a loop and wherein the sheet of drug-releasingmaterial spans a majority of the coil or loop area upon deployment ofthe retention structure.
 11. The ureteral stent of claim 1, comprising asheet of drug-releasing material connected to a sleeve of material thatis disposed over at least a portion of the deployable retentionstructure.
 12. The ureteral stent of claim 11, wherein the sheet is abiodisintegrable sheet.
 13. The ureteral stent of claim 11, wherein thesleeve is a heat shrinkable sleeve.
 14. The ureteral stent of claim 1,wherein the retention structure is a kidney retention structureconfigured to be delivered through the ureter and deployed in thekidney.
 15. The ureteral stent of claim 14, wherein the retentionstructure is adapted to be reduced to a profile that is sufficientlysmall during deployment to allow the retention structure to be deliveredto the kidney.
 16. The ureteral stent of claim 1, wherein the retentionstructure comprises a plurality of elongated elements to which the sheetof drug-releasing material is attached and between which the sheet ofdrug-releasing material is situated upon deployment of the retentionstructure.
 17. The ureteral stent of claim 1, wherein the stent body anddeployable retention structure comprise a biostable polymer.
 18. A kitcomprising (a) a ureteral stent comprising an elongated stent body and adeployable retention structure and (b) at least one drug-releasingmember selected from (i) a sleeve of drug-releasing material that isconfigured to be disposed over the stent body and (ii) a sheet ofdrug-releasing material that is configured to be connected to the stentbody, and (c) optionally, a delivery device, a guidewire, or both. 19.The kit of claim 18, wherein the components are provided in a sterilepackage.
 20. A method of treatment comprising administering a ureteralstent to a patient in need of treatment, said ureteral stent comprisingan elongated stent body, a deployable retention structure, and adrug-releasing member selected from (i) a sleeve of drug-releasingmaterial that is disposed over at least a portion of the deployableretention structure, (ii) a sheet of drug-releasing material that isattached to the deployable retention structure and (iii) a sheet ofdrug-releasing material connected to a sleeve of material that isdisposed over at least a portion of the deployable retention structure.